Nitrosated and nitrosylated heme proteins

Abstract

Nitrosylation of proteins and amino acid groups enables selective regulation of protein function, and also endows the proteins and amino acids with additional smooth muscle relaxant and platelet inhibitory capabilities. Thus, the invention relates to novel compounds achieved by nitrosylation of protein thiols. Such compounds include: S-nitroso-t-PA, S-nitroso-cathepsin; S-nitroso-lipoprotein; and S-nitroso-immunoglobulin. The invention also relates to therapeutic use if S-nitroso-protein compounds for regulating protein function, cellular metabolism and effecting vasodilation, platelet inhibition, relaxation of non-vascular smooth muscle, and increasing blood oxygen transport by hemoglobin and myoglobin. The compounds are also used to deliver nitric oxide in its most bioactive form in order to achieve the effects described above, or for in vitro nitrosylation of molecules present in the body. The invention also relates to the nitrosylation of oxygen, carbon and nitrogen moieties present on proteins and amino acids, and the use thereof to achieve the above physiological effects.

What is claimed is:  
     
       1. A nitrosated and/or nitrosylated heme protein, wherein the heme protein is nitrosated and/or nitrosylated at one or more thiol groups in the heme protein. 
     
     
       2. The nitrosated and/or nitrosylated heme protein of claim  1 , wherein the heme protein is hemoglobin. 
     
     
       3. The nitrosated and/or nitrosylated heme protein of claim  2 , wherein the hemoglobin is a human hemoglobin. 
     
     
       4. The nitrosated and/or nitrosylated heme protein of claim  2 , wherein the hemoglobin is bovine hemoglobin. 
     
     
       5. A pharmaceutical composition comprising the nitrosated and/or nitrosylated heme protein of claim  1  and a pharmaceutically acceptable carrier. 
     
     
       6. A pharmaceutical composition of claim  5 , further comprising at least one of a nonionic surfactant, a phospholipid, an emulsifier or a fatty acid.